Diabetes mellitus can be a devastating disease, particularly when considering the complications of foot ulceration and amputation. With this proposal we will better understand how the disease process of diabetes alters the cellular and matrix level properties of the plantar soft tissue, which in turn affects the mechanical properties of the tissue. We will also explore differences in the plantar soft tissue characteristics due to tissue location (i.e., the ball of the foot versus the heel) and specimen age (i.e., young versus old). The long- term goal of this research is to reduce the incidence of lower extremity ulceration and amputation by using the knowledge gained to alter the stress distribution beneath diabetic feet with improved foot orthoses, or perhaps to initiate a cellular/matrix level treatment that alters the tissue mechanical properties. We will work towards this goal by completing the specific aims of this study, which include: [1] assess the mechanical properties of 1) older diabetic, 2) older non-diabetic, and 3) younger non-diabetic plantar soft tissue at six different locations beneath the foot, [2] assess the cellular/matrix properties of 1) older diabetic, 2) older non- diabetic, and 3) younger non-diabetic plantar soft tissue at six different locations beneath the foot and [3] determine how the mechanical and cellular/matrix properties of the plantar soft tissue are related. This research will increase our fundamental understanding of the disease process and implementing the knowledge gained will reduce the burden of ulceration and amputation on diabetic patients. This study is designed with a between-group component examining the effect of diabetes and age on the tissues and a repeated measures component addressing the effect of tissue location. Previous research supports the hypothesized changes in the mechanical (increased stiffness) and cellular/matrix (increased collagen and collagen cross-linking) properties due to diabetes, tissue location or age, however there has not been a systematic study of how these properties interact. We will conduct mechanical testing, using state-of-the-art materials testing machines, while all cellular/matrix testing will employ well-established protocols. There are over 18 million Americans with diabetes, accounting for over 80,000 non-traumatic amputations each year between 1996 and 2002. Thus, not only is there a large diabetic population in the United States (> 6%), but they also account for a disproportional amount (>60%) of all non-traumatic lower extremity amputations. [unreadable] [unreadable]